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In addition, the effects of aripiprazole on D<jats:sub>2<\/jats:sub>and D<jats:sub>3<\/jats:sub>receptors were tested and compared with previously reported cariprazine data.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000894_abs2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>Rats received vehicle, aripiprazole (2, 5, or 15 mg\/kg), or cariprazine (0.06, 0.2, or 0.6 mg\/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu\u2013M), caudate-putamen lateral (CPu\u2013L), hippocampal CA1 (HIPP\u2013CA1) and CA3 (HIPP\u2013CA3) regions, and the entorhinal cortex (EC).<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000894_abs3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Similar to previous findings with cariprazine, aripiprazole upregulated D<jats:sub>2<\/jats:sub>receptor levels in various regions; D<jats:sub>3<\/jats:sub>receptor changes were less than those reported with cariprazine. All aripiprazole doses and higher cariprazine doses increased 5-HT<jats:sub>1A<\/jats:sub>receptors in the MPC and DFC. Higher aripiprazole and all cariprazine doses increased 5-HT<jats:sub>1A<\/jats:sub>receptors in HIPP\u2013CA1 and HIPP\u2013CA3. Aripiprazole decreased 5-HT<jats:sub>2A<\/jats:sub>receptors in the MPC, DFC, HIPP\u2013CA1, and HIPP\u2013CA3 regions. Both compounds decreased NMDA receptors and increased AMPA receptors in select brain regions.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000894_abs4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Long-term administration of aripiprazole and cariprazine had similar effects on 5-HT<jats:sub>1A<\/jats:sub>, NMDA, and AMPA receptors. However, cariprazine more profoundly increased D<jats:sub>3<\/jats:sub>receptors while aripiprazole selectively reduced 5-HT<jats:sub>2A<\/jats:sub>receptors. These results suggest that the unique actions of cariprazine on dopamine D<jats:sub>3<\/jats:sub>receptors, combined with its effects on serotonin and glutamate receptor subtypes, may confer the clinical benefits, safety, and tolerability of this novel compound in schizophrenia and bipolar mania.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1092852916000894","type":"journal-article","created":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T10:49:06Z","timestamp":1483699746000},"page":"484-494","source":"Crossref","is-referenced-by-count":18,"title":["Long-term effects of aripiprazole exposure on monoaminergic and glutamatergic receptor subtypes: comparison with cariprazine"],"prefix":"10.1017","volume":"22","author":[{"given":"Yong 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